The present invention relates to a process for producing optically active compounds in which particular alcohols are reacted with enzymes by a biochemical technique.
Compounds represented by the general formula: ##STR2## are useful chemical compounds as starting materials for pharmaceuticals, agricultural chemicals and the like, and as intermediates. (In formula I, X is selected from halogen atoms, e.g., chlorine, flourine, and bromine, and a cyano group; Y is selected from halogen atoms, e.g., chlorine, flourine, and bromine, a cyano group, a trifluoromethyl group, an amino group, an alkylamino group, an alkyloxycarbonyl group and groups of the following formula: ##STR3## wherein Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4, Z.sup.5 are selected from hydrogen and halogen atoms, a cyano group, a trifluoromethyl group, an amino group, an alkylamino group, an aryloxy group, alkyl and alkoxy groups having 1-20 carbon atoms, and groups of the following formula: ##STR4## wherein W.sup.1, W.sup.2, W.sup.3, W.sup.4 and W.sup.5 are selected from hydrogen, halogen atoms, a cyano group, a trifluoromethyl group, an amino group, an alkylamino group, and alkyl and alkoxy groups having 1-20 carbon atoms; and R is an alkylene group having 1-20 carbon atoms; and n is 0 or 1.) However, the compounds have optical isomers, and in many cases they do not sufficiently exhibit their useful characteristics unless the R- or S-alcohol is preponderant.
For the above reasons, and in order to obtain an optically active substance, it is necessary to optically resolve a racemate (itself typically obtained by a synthetic chemical technique), to conduct an asymmetric synthesis, or to convert from an optically active starting material by a stereochemical synthetic method. In many cases, the process is troublesome and disadvantageous industrially.
Accordingly, it is desired to develop a technique for obtaining optically active compounds by an industrially advantageous method.
As a known biochemical technique, for example, there is a method described in Japanese Publication of Unexamined Patent Application No. 59-205989 in which a racemic ester is hydrolyzed with a lipase and a desired alcohol is obtained. In this case, the racemic ester is often insoluble in water, so that it is necessary to emulsify or stir vigorously, using a large quantity of water. Furthermore, as enzyme is water-soluble and unstable to moisture, immobilized enzyme is required so as to act stably and to be easily removed or reused after the reaction.
Klibanov et al. reported a method in which enzyme powder was directly added into a reaction system (J. Am. Chem. Soc., 107, 7072(1985)). In this case, esters for transesterification are extremely limited and 2,2,2-trichloroethyl butyrate is used as the ester. Furthermore, it is essential to use an organic solvent, such as heptane, and ether which has many problems when it is used industrially.